**13. Photodynamic therapy in combination with sonodynamic therapy**

The exploratory clinical study of PDT combined with sonodynamic therapy (SDT) against cholangiocarcinoma in which hematoporphyrin was used as the sono-photosensitizer provides a clear indication of the state of this technology in the clinical translation trajectory [117]. This is supported by the clinical pilot studies [118] and case reports [119] that are starting to appear in the literature. Nanotechnology is ubiquitous not only as a platform for the PDT and SDT agents [120, 121], but also for other purposes of the innovation, such as hypoxia amelioration, disease targeting, imaging-guided therapy, and stimulus-responsive release. For example, reducing human serum albumin to cleave the disulfide linkages and produce free thiol groups, followed by conjugation with hemoglobin, was used to produce a nanoplatform capable of carrying oxygen. The innovative nanoplatform was used to encapsulate manganese (II) phthalocyanine as the PS and to absorb copious amount of oxygen before administration as a sono-photosensitizer that responds to light and ultrasonic activation to produce ROS, even from the insufficiently oxygenated tumor microenvironments of 4 T1 breast cancer xenografts in mice. It also enabled magnetic resonance and photoacoustic imaging [122]. Additionally, although notoriously difficult to reach by PDT, brain cancer can be reached with SDT. The PS 3-(1′-Hexyloxy)ethyl-3-devinylpyropheophorbide-a, delivered using cationic polyacrylamide NPs functionalized with tetramethyl ammonium groups, improved the kill rate of the combination of PDT and SDT relative to the individual technologies, against the U87 human glioblastoma cell line, considered to be the best model for brain cancer [123].

### **14. Photodynamic therapy in combination with magnetic hyperthermia**

Enabled by a whole-body applicator, MH is used to treat cancerous tumors that are difficult to reach, such as tumors in the brain and those located in dark tissues, such as the liver, spleen, pancreas, and bones [124]. Recently, however, the development of a handheld MH device has been reported for more focused treatments [125].

#### *Important Advances in Antibacterial Nanoparticle-Mediated Photodynamic Therapy DOI: http://dx.doi.org/10.5772/intechopen.113340*

Nanoconjugate platforms for the combination of PDT with MH need to incorporate the PS and magnetic NPs ideally in the same nanoconjugate [87]. For example, using nanoemulsions loaded with magnetic iron oxide NPs and an aluminum phthalocyanine PS, the combination of MH and PDT was reported to achieve 66% reduction in the viability of the human bone marrow mesenchymal stem cell line [126]. In addition, there are examples of multifunctional nanotechnology platforms aimed at combining PDT with MH that are selective for cancer cells. For example, a nanoconjugate of Janus nanobulets with magnetic manganese oxide heads and chlorin-e6 PS-laden mesoporous silica bodies was cloaked with the breast cancer cell membrane. Following rapid cancer cell endocytosis, the disulfide anchor of the PS onto the mesoporous silica side of the Janus nanobulet was easily cleaved upon the pH drop of the breast cancer cell internal microenvironment, thus releasing the PS [127].
